Stimulation of corticosterone secretion in vitro by brief ACTH exposure

We examined the relationship between ACTH concentration and exposure duration on stimulation of corticosterone (B) secretion in vitro using perifused enzymatically dispersed rat adrenocortical cells. A modular perifusion apparatus was used that permitted evaluation of 20-24 cell chambers per experimental session. In expt 1, 20-1000 pg/ml concentrations of synthetic ACTH-(1-24) were presented to cells for 1 min. In expt 2, 100 pg ACTH-(1-24) was presented to adrenal cells in five dose-duration regimens ranging from 5 pg/min for 20 min to 100 pg/min for 1 min. Perifusal rate was 1 ml/min in all sessions. B was determined by radioimmunoassay. In expt 1 (constant-duration paradigm), 1-min presentation of ACTH-(1-24) produced log-linear dose-response effects across these concentrations (r = 0.926, P less than 0.01). In expt 2 (constant-mass paradigm), identical masses administered in different dose-duration regimens had different steroidogenic efficacies (P less than 0.02): low-dose long-duration regimens provoked greater total release than high-dose short-duration regimens. Overall, every dose-duration regimen was associated with stimulation of B secretion. These results indicate that very brief exposure to physiological concentrations of ACTH-(1-24) is a significant stimulus for corticosteroid secretion; variations in the dose-duration regimen over the physiological range modifies both the maximum rate of secretion and the duration of secretion, but not the response latency; and ACTH-(1-24) presentation mass is not the sole determinant of B secretion.